chr1-207124331-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000715.4(C4BPA):c.671T>C(p.Ile224Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,613,690 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.014 ( 52 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 44 hom. )
Consequence
C4BPA
NM_000715.4 missense
NM_000715.4 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -2.42
Genes affected
C4BPA (HGNC:1325): (complement component 4 binding protein alpha) This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. Along with a single, unique beta-chain, seven identical alpha-chains encoded by this gene assemble into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. Two pseudogenes of this gene are also found in the cluster. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004507065).
BP6
?
Variant 1-207124331-T-C is Benign according to our data. Variant chr1-207124331-T-C is described in ClinVar as [Benign]. Clinvar id is 783303.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2059/152246) while in subpopulation AFR AF= 0.0459 (1907/41532). AF 95% confidence interval is 0.0442. There are 52 homozygotes in gnomad4. There are 998 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 52 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C4BPA | NM_000715.4 | c.671T>C | p.Ile224Thr | missense_variant | 6/12 | ENST00000367070.8 | |
C4BPA | XM_005273251.3 | c.671T>C | p.Ile224Thr | missense_variant | 6/12 | ||
C4BPA | XM_005273252.5 | c.671T>C | p.Ile224Thr | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C4BPA | ENST00000367070.8 | c.671T>C | p.Ile224Thr | missense_variant | 6/12 | 1 | NM_000715.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0135 AC: 2056AN: 152128Hom.: 52 Cov.: 32
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GnomAD3 exomes AF: 0.00351 AC: 880AN: 250444Hom.: 23 AF XY: 0.00270 AC XY: 365AN XY: 135350
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GnomAD4 exome AF: 0.00142 AC: 2077AN: 1461444Hom.: 44 Cov.: 33 AF XY: 0.00122 AC XY: 885AN XY: 727052
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GnomAD4 genome ? AF: 0.0135 AC: 2059AN: 152246Hom.: 52 Cov.: 32 AF XY: 0.0134 AC XY: 998AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at